The fastest growing segment of the US population is the oldest old, people 85 years and older. Four out of ten of these individuals experience cognitive impairment, such as memory loss or impaired reasoning, leading to disability and dependency on others for assistance. Thus the ability to treat dementia in its very early stages, delay its onset, or even prevent it, is becoming ever more vital. Yet, as this demand increases, the nature of cognitive impairment in the oldest old is still poorly understood. The Oregon Brain Aging Study (OBAS), by studying a large group of oldest old individuals, following each individual's progress from year to year, endeavors to address the following questions: 1) Of the oldest old who do not have conditions known to cause cognitive impairment, what proportion of these people develop the early symptoms of dementia, and how many of those progress to clear dementia? 2) Can it be predicted, before any symptoms develop, who will develop dementia? 3) Do physical changes in the brain detected at autopsy explain dementia in the oldest old? Funded by a VA Merit Review Grant, OBAS has begun to answer these questions. In the first years of the study, we established characteristics of the healthy oldest old; we now know how the optimally functioning elder performs on cognitive and neurological tests and what are the characteristic features of their genetics and MRI brain scans. This descriptive information is unique, as elderly individuals without the diseases associated with age have never before been adequately described. This is essential to developing a clear understanding of the distinctions between changes in the elderly which are a part of healthy aging, in contrast to changes caused by age-associated diseases. Our database has become a resource for many other scientists at the Portland VAMC, the Oregon Health Sciences University (OHSU), and nationally. Moreover, this bank of data will become increasingly valuable since three out of four of our subjects have volunteered to donate their brains for autopsy, and DNA samples from every subject are available for current and future research into the genetic factors affecting the oldest old. Although all the subjects in OBAS are free of cognitive impairment when they enter the study, a striking proportion of them (44%) developed definite signs of early dementia within just four years. Looking back at the data obtained before the subjects began to dement, we have found that even several years before the symptoms were apparent, these subjects' performance on certain memory tests differed from the elders who did not go on to dement. Also, the subjects with early dementia can be detected using MRI scans of the brain, since specific areas of the brain atrophy more quickly with dementia than in healthy aging.